Protein Levels Research Articles

Maximum Diameter of Ileocecal Lymph Nodes Measured Using Abdominal Ultrasonography Allows for the Discrimination of Yersinia pseudotuberculosis Infection from Kawasaki Disease.

This study aimed to determine whether the maximum diameter of ileocecal lymph nodes measured using abdominal ultrasonography is useful for differentiating Yersinia pseudotuberculosis infection from Kawasaki disease in the acute phase. The optimal maximum diameter cutoff of the ileocecal lymph nodes was also explored to optimize differentiation between these 2 diseases. We included pediatric patients <15 years old who met the diagnostic criteria for Kawasaki disease. Stool culture testing, loop-mediated isothermal amplification of stool specimens, and serological diagnosis were performed to confirm the presence or absence of Y. pseudotuberculosis infection. Of the 122 patients included in the analysis, 17 were confirmed to have Y. pseudotuberculosis infection and 105 were not. The age (in months), white blood cell count, C-reactive protein level, prediction score (risk score) for nonresponse to intravenous immunoglobulin, and number of intravenous immunoglobulin doses did not differ significantly between the Y. pseudotuberculosis-positive and -negative groups. The maximum diameter of ileocecal lymph nodes was 6.0 (5.5-9.5) mm in the Y. pseudotuberculosis-positive group and 3.0 (2.5-3.8) mm in the Y. pseudotuberculosis-negative group (numbers presented as median, interquartile range), with a significantly larger diameter in the Y. pseudotuberculosis-positive group (P < 0.01, Mann-Whitney U test), suggesting potency of ultrasonography. In patients meeting the diagnostic criteria for Kawasaki disease, the possibility of Y. pseudotuberculosis infection is significantly higher if the maximum ileocecal lymph node diameter ≥5.1 mm. Its sensitivity and specificity being 100%, and 89.5%, respectively.

Interleukin-9 promotes EMT-mediated PM2.5-induced pulmonary fibrosis by activating the STAT3 pathway.

This study investigated the impact of PM2.5 on promoting EMT in PM2.5-induced pulmonary fibrosis (PF) development and explored molecular mechanisms of the IL-9/STAT3/Snail/TWIST1 signaling pathway in PF owing to PM2.5. Four groups of male SD rats were formed: control (0mg/kg.bw), low (1mg/kg.bw), medium (5mg/kg.bw), and high-dose (25mg/kg.bw) PM2.5 groups. Experimental rats were subjected to PM2.5 exposure via intratracheal instillation, given once weekly for 16weeks. 24 h after the final exposure, blood, BALF, and lung tissues were collected. Pulmonary epithelial cells underwent cultivation and exposure to varying PM2.5 concentrations with/without inhibitors for 24h, after which total protein was extracted for relevant protein assays. The findings demonstrated that PM2.5 damaged lung tissue to different degrees and led to PF in rats. Rats subjected to PM2.5 exposure exhibited elevated concentrations of IL-9 protein in both serum and BALF, and elevated levels of IL-9 and its receptor, IL-9R, in lung tissues, compared to control counterparts. Furthermore, PM2.5-exposed groups demonstrated significantly augmented protein levels of p-STAT3, Snail, TWIST1, Vimentin, COL-I, and α-SMA, while displaying notably diminished levels of E-Cadherin compared to control group. The same findings were observed in PM2.5-treated cells. In BEAS-2B cells co-treated with Stattic (STAT3 inhibitor) and PM2.5, the opposite results occurred. Similar results were obtained for cells co-treated with IL-9-neutralizing antibody and PM2.5. Our findings suggest PM2.5 mediates PF development by promoting IL-9 expression, leading to STAT3 phosphorylation and upregulation of Snail and TWIST1 expression, triggering EMT occurrence and progression in lung epithelial cells.

Pyrroloquinoline Quinone Alleviates Mitochondria Damage in Radiation-Induced Lung Injury in a MOTS-c-Dependent Manner.

Radiation-induced lung injury (RILI) is a prevalent complication of thoracic tumor radiotherapy and accidental radiation exposure. Pyrroloquinoline quinone (PQQ), a novel vitamin B, plays a crucial role in delaying aging, antioxidation, anti-inflammation, and antiapoptosis. This study aims to investigate the protective effect and mechanisms of PQQ against RILI. C57BL/6 mice were exposed to a 20 Gy dose of X-ray radiation on the entire thorax with or without daily oral administration of PQQ for 2 weeks. PQQ effectively mitigated radiation-induced lung tissue damage, inflammation, oxidative stress, and epithelial cell apoptosis. Additionally, PQQ significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells. Mechanistically, PQQ upregulated the mRNA and protein levels of MOTS-c in irradiated lung tissue and MLE-12 cells. Knockdown of MOTS-c by siRNA substantially attenuated the protective effects of PQQ on oxidative stress, inflammation, and apoptosis. In conclusion, PQQ alleviates RILI by preserving mitochondrial function through a MOTS-c-dependent mechanism, suggesting that PQQ may serve as a promising nutraceutical intervention against RILI.

MiR-19-3p/GRSF1/COX1 axis attenuates early brain injury via maintaining mitochondrial function after subarachnoid haemorrhage

BackgroundGuanine-rich RNA sequence binding factor 1 (GRSF1) is an RNA-binding protein, which is eventually localised to mitochondria and promotes the translation of cytochrome C oxidase 1 (COX1) mRNA. However, the...

Association of novel DNAH11 variants with asthenoteratozoospermia lead to male infertility

BackgroundBi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown.MethodsA collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants.ResultsIn this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants.

Effect of fibroblasts small- conductance Ca2+ -activated potassium channel subtype 2 (SK2) on myocardial fibrosis in pressure overload mouse

Studies have shown that Small conductance Ca2 + −activated K+ (SK) channel are expressed in fibroblasts. We aimed to determine the expression of SK2 channels in cardiac fibroblasts during myocardial hypertrophy and investigate its relationship with fibrotic remodeling. Myocardial hypertrophy and fibrotic remodeling induced by transverse aortic constriction (TAC) were assessed by echocardiography, Masson's trichrome staining and Western blot. Knockdown and overexpression of the SK2 protein were used to assess relationship between SK2 expression in fibroblasts and myocardial fibrosis. There is a positive correlation between myocardial fibrosis and SK2 channel protein expression during the development of myocardial hypertrophy. The differentiation and secretion of fibroblasts in mice with cardiac hypertrophy are enhanced, and the expression of SK2 channel protein is increased. Manipulating SK2 levels in fibroblasts can either promote or inhibit their differentiation and secretory function. Knocking down SK2 reduces the up-regulation of TGF β1, p-Smad2/3/GAPDH, p-p38/GAPDH, p-ERK1/2/GAPDH, and p-JNK/GAPDH proteins induced by Ang II in cardiac fibroblasts without significantly affecting total protein levels. AAV9-SK2-RNAi injection in mice improves cardiac function. Collectively, our study suggests that the expression of the SK2 channel is significantly increased in fibroblasts of mice with myocardial hypertrophy, potentially impacting myocardial fibrosis remodeling via the TGF-β signaling pathway.

NaV1.1 contributes to the cell cycle of human mesenchymal stem cells by regulating AKT and CDK2.

Non-excitable cells express sodium voltage-gated channel alpha subunit 1 gene and protein (SCN1A/NaV1.1); however, the functions of NaV1.1 are unclear. SCN1A was expressed in human mesenchymal stem cells (MSCs). Nav1.1 was abundantly expressed in the endoplasmic reticulum of MSCs; however, its expression was not found to be related to sodium currents. SCN1A-silencing reduced MSC proliferation and delayed the cell cycle in the S phase. SCN1A-silencing also suppressed the protein levels of CDK2 and AKT, despite similar mRNA expression, and inhibited AKT phosphorylation in MSCs. Cycloheximide-chase assay showed that SCN1A-silencing induced CDK2 but not AKT protein degradation in MSCs. Proteolysis inhibition assay using epoxomicin, bafilomycin A1, and NH4Cl, revealed that the ubiquitin-proteasome and autophagy/endo-lysosome systems were irrelevant to CDK2 and AKT protein reduction in SCN1A-silenced MSCs. AKT inhibitor LY294002 did not affect the degradation and nuclear localization of CDK2 in MSCs. Likewise, AKT activator SC79 did not attenuate the SCN1A-silencing effects on CDK2 in MSCs. These results suggest that NaV1.1 contributes to the cell cycle of MSCs by regulating the post-translational control of AKT and CDK2.

Minocycline alleviates lipopolysaccharide-induced cardiotoxicity by suppressing the NLRP3/Caspase-1 signaling pathway.

Minocycline (Min), as an antibiotic, possesses various beneficial properties such as anti-inflammatory, antioxidant, and anti-apoptotic effects. Despite these known qualities, the precise cardioprotective effect and mechanism of Min in protecting against sepsis-induced cardiotoxicity (SIC) remain unspecified. To address this, our study sought to assess the protective effects of Min on the heart. Lipopolysaccharide (LPS) was utilized to establish a cardiotoxicity model both in vivo and in vitro. Min was pretreated in the models. In the in vivo setting, evaluation of heart tissue histopathological injury was performed using hematoxylin and eosin (H&E) staining and TUNEL. Immunohistochemistry (IHC) was employed to evaluate the expression levels of NLRP3 and Caspase-1 in the heart tissue of mice. During in vitro experiments, the viability of H9c2 cells was gauged utilizing the CCK8 assay kit. Intracellular ROS levels in H9c2 cells were quantified using a ROS assay kit. Both in vitro and in vivo settings were subjected to measurement of oxidative stress indexes, encompassing glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Additionglly, myocardial injury markers like lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) activity were quantified using appropriate assay kits. Western blotting (WB) analysis was conducted to detect the expression levels of NOD-like receptor protein-3 (NLRP3), caspase-1, IL-18, and IL-1β, alongside apoptosis-related proteins such as Bcl-2 and Bax, and antioxidant proteins including superoxide dismutase-1 (SOD-1) and antioxidant proteins including superoxide dismutase-1 (SOD-2), both in H9c2 cells and mouse heart tissues. In vivo, Min was effective in reducing LPS-induced inflammation in cardiac tissue, preventing cell damage and apoptosis in cardiomyocytes. The levels of LDH and CK-MB were significantly reduced with Min treatment. In vitro studies showed that Min improved the viability of H9C2 cells, reduced apoptosis, and decreased ROS levels in these cells. Further analysis indicated that Min decreased the protein levels of NLRP3, Caspase-1, IL-18, and IL-1β, while increasing the levels of SOD-1 and SOD-2 both in vivo and in vitro. Min alleviates LPS-induced SIC by suppressing the NLRP3/Caspase-1 signalling pathway in vivo and in vitro.

Morin promotes autophagy in human PC3 prostate cancer cells by modulating AMPK/mTOR/ULK1 signaling pathway

AMP-activated protein kinase (AMPK) suppresses tumorigenesis by modulating autophagy and apoptosis. This study evaluated the impact of Morin on PC3 prostate cancerous cells by examining the AMPK/ mechanistic target of rapamycin (mTOR)/ ULK1 (UNC-51-like kinase 1) pathway and autophagy process. The PC3 cells were treated with Morin (50 µg/ml) and AICAR (an AMPK activator). Cell viability, apoptosis, autophagy, and level of phosphorylated and non-phosphorylated ULK1, AMPK, and mTOR, as well as LC3B/LC3A, have been investigated. Through DAPI staining, measurement of Bax/Bcl-2 ratio, Caspase activity, and Annexin V/PI method, it has been revealed that Morin induces apoptosis and reduces the growth of PC3 cells. Morin enhanced the protein level of phosphorylated AMPK (p-AMPK) and ULK1 (p-ULK1) and decreased the expression of phosphorylated mTOR (p-mTOR) in the PC3 cells. Morin could also increase the LC3B/LC3A ratio, Acridine Orange-positive cells, expression of Beclin-1 and ATG5 genes, and decrease the p62 protein level indicating autophagy-inducing. AICAR (an AMPK activator) enhanced the impact of Morin on apoptosis, cell growth, and expression of LC3B, p-AMPK, p-ULK1, and p-mTOR proteins in the PC3 cells. These findings suggest that Morin induces apoptotic and autophagic cell death by activating AMPK and ULK1 and suppressing mTOR pathways.

DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain

BackgroundPlasma growth differentiation factor 15 (GDF15) and N‐terminal proB‐type natriuretic peptide (NT‐proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification.ResultsIn the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all PFDR < 0.05). Bayesian epigenome-wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] > 95%) with levels of GDF15 and NT-proBNP, respectively. EpiScores for GDF15 and NT-proBNP were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (hazard ratios (HR) range 1.36–1.41, PFDR < 0.05). The EpiScore for NT-proBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R2 range of 5.7–12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population.ConclusionsEpiScores for serum levels of GDF15 and Nt-proBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification.

Effects of Indobufen Combined with Clopidogrel on Left Ventricular Function and Inflammatory Factors in Patients after PCI

Background: Percutaneous intracoronary intervention (PCI) is the preferred method for treating coronary heart disease. However, the insufficient coagulation function after the procedure may lead to poor vascular reperfusion, thereby affecting cardiac function. Indobufen and clopidogrel have antiplatelet and anti-inflammatory effects, but the impact of their combined use on left ventricular function and inflammatory factors in patients after PCI remains unclear. This study aimed to explore the influence of indobufen combined with clopidogrel on left ventricular function and inflammatory factors in patients after PCI. Methods: Medical records of 100 patients who underwent PCI surgery were selected for retrospective analysis. Their admission time ranged from January 2022 to June 2023. All research subjects who met the inclusion criteria were assigned to two groups according to different treatment methods with 57 cases in the control and 43 cases in the observation. The left ventricular function, inflammatory factors, coagulation function levels, and occurrence of complications were compared between the two groups. Results: After going through treatment, the levels of left ventricular end-diastolic volume, left ventricular end-systolic diameter, and left ventricular end-diastolic diameter of the observation group were significantly lower than those of the control. The ejection fraction significantly increased in the observation group, and the difference between two groups was significant (p &lt; 0.05). Furthermore, the level of high-sensitivity C-reactive protein in the observation was significantly lower than that of the control benefiting from treatment with a significant difference (p &lt; 0.05). The activated partial thromboplastin time, prothrombin time, and thrombin time levels of all patients significantly increased (p &lt; 0.05) with no difference between the two groups (p &gt; 0.05). The complication rate in the control patients was 17.54% (10/57), and that in the observation patients was 9.30% (4/43). No significant difference existed between the two groups (p &gt; 0.05). Conclusions: Indobufen combined with clopidogrel treatment for patients after PCI significantly improved left ventricular function, inhibited inflammatory response, enhanced coagulation function, and had high safety. These results can provide some basis for the treatment of patients after clinical PCI.

Elevated Serum IL-17A in Kawasaki Disease Patients Predicts Responsiveness to Intravenous Immunoglobulin Therapy

Introduction: This study aimed to investigate the correlation between serum interleukin (IL)-17A levels and responsiveness to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD) patients. Methods: A retrospective analysis on data from 192 KD patients admitted to the Anqing Municipal Hospital between January 2021 and January 2024 was conducted. Patients were categorized into IVIG-nonresponsive and IVIG-sensitive groups as per the treatment outcomes. Outcome measures included serum IL-17A levels, left coronary artery (LCA) Z scores, and relevant laboratory parameters. Logistic regression analysis was performed to identify predictive factors for IVIG responsiveness, and diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC). Results: A total of 40 IVIG-nonresponsive cases and 152 IVIG-sensitive cases were included. Prior to intervention, IVIG-nonresponsive patients had significantly higher serum IL-17A levels compared to IVIG-sensitive patients, with a statistically significant difference. After intervention, serum IL-17A levels significantly decreased in IVIG-sensitive patients while remaining elevated in IVIG-nonresponsive patients. IVIG-nonresponsive patients exhibited significantly higher levels of C-reactive protein (CRP), white blood cell count (WBC), NE, and ALT compared to IVIG-sensitive patients, whereas no significant differences in LCA Z scores between the two groups existed. Multivariable logistic regression analysis identified pre-IL-17A, CRP, WBC, and ALT as independent predictors of IVIG-nonresponsiveness in KD. When pre-IL-17A was ≥39.96 pg/mL, the specificity and sensitivity for predicting IVIG-nonresponsive KD were 63.9% and 71.9%, respectively, with an AUC of 0.637. The combined diagnosis of IL-17A, CRP, WBC, and ALT yielded an AUC of 0.780. Conclusion: Serum IL-17A levels were remarkably elevated in IVIG-nonresponsive KD patients both before and after intervention. A serum IL-17A level (≥39.96 pg/mL) demonstrated good predictive profile for IVIG-nonresponsive KD, and combining IL-17A with CRP, WBC, and ALT improved diagnostic performance.

USP33 facilitates the ovarian cancer progression via deubiquitinating and stabilizing CBX2.

Post-translational modifications of proteins play a pivotal role in both the initiation and progression of ovarian cancer. Despite the recognition of USP33 as a significant factor in various cancers, its specific function and underlying mechanisms in ovarian cancer remain elusive. Proteomics and ubiquitinomics approaches were coupled to screen novel substrate proteins directly regulated by USP33. Our findings unveil that USP33 was observed to eliminate K27- and K48-linked ubiquitin chains from CBX2 at the K277 position. Notably, acetylation of CBX2 at K199, catalyzed by lysine acetyltransferase GCN5, was found to enhance its interaction with USP33, subsequently promoting further deubiquitination and stabilization. Functionally, our experiments demonstrate that USP33 significantly enhances ovarian cancer proliferation and metastasis in a CBX2-dependent manner. Furthermore, analysis revealed a direct positive correlation between the expression levels of USP33 and CBX2 proteins in human specimens, with elevated levels being associated with reduced survival rates in ovarian cancer patients. These findings elucidate the mechanism by which USP33 augments ovarian cancer progression through the stabilization of CBX2, underscoring the USP33-CBX2 axis as a promising therapeutic target in ovarian cancer management.

Yak DEFB123 alleviates lung injury caused by Klebsiella pneumoniae through MAPKs signaling pathway

Beta-defensins, such as β-defensin 123 (DEFB123), are vital components of the immune system's defense against infections due to their strong antimicrobial properties and capacity for modulating the body's immunological responses. In this study, we successfully cloned and analyzed the yak DEFB123 gene sequence. Subsequently, we obtained recombinant protein DEFB123 (rDEFB123) through prokaryotic expression. Our results demonstrate that rDEFB123 effectively inhibits the growth of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. Furthermore, rDEFB123 enhances the phagocytic activity of macrophages by regulating specific factors. In a mouse model infected with Klebsiella pneumoniae, the administration of rDEFB123 showed significantly lower levels of serum ALT and AST compared to the control group. Moreover, IFN-γ and IgG were significantly increased in the rDEFB123-treated groups, indicating an enhanced immune response. In the MAPKs signaling pathway of the infected mouse lungs, the expressions of JNK, TRAF2, TRAF6, MIF, and IL-1β genes were downregulated in the rDEFB123-treated groups. Moreover, the levels of p-JNK protein were significantly decreased in these groups as well. Klebsiella pneumoniae caused systemic infection with organ damage in mice. However, the administration of rDEFB123 suppressed the expressions of inflammatory factors, thereby mitigating organ injury and regulating the activity of apoptosis-related factors to enhance immunity. These findings provide valuable theoretical data for future exploration of the functionality and potential applications of DEFB123 in yak.

Gender differences in the relationship between the triglyceride-glucose index and serum Klotho concentrations among the middle-aged and elderly: a cross-sectional analysis

BackgroundThe triglyceride-glucose (TyG) index is recognized as a robust indicator for evaluating insulin resistance (IR). Despite the well-documented anti-aging biological functions of Klotho protein, its correlation with the TyG index remains unexplored.MethodsA cross-sectional analysis was conducted involving participants from the National Health and Nutrition Examination Surveys (NHANES) 2007–2016. The TyG index was computed using laboratory data, while serum Klotho concentrations was determined using ELISA kit. After adjusting potential confounding variables, multivariate regression models were employed to evaluate the association between the TyG index and Klotho protein levels among middle-aged and elderly females and males separately. Additionally, smooth curve fitting and segmented regression model were applied to investigate potential threshold effects and identify the inflection point.ResultsA total of 6,573 adults qualified for inclusion, comprising 3,147 (47.88%) males and 3,426 (52.12%) females. Multivariate regression analysis revealed that females with a higher TyG index exhibited significantly lower serum Klotho concentrations (β=-83.41, 95% CI: -124.23 to -42.60, P < 0.0001). This association was not statistically significant in males (β = 15.40, 95% CI: -19.16 to 49.95, P = 0.3827). Subgroup analyses revealed a significant interaction effect by diabetes status in females (P-interaction = 0.0121), where non-diabetic females showed a stronger negative association between TyG index and serum Klotho levels compared to diabetic females. In the female group, when TyG index was divided into quartiles, individuals in the highest quartile of TyG index exhibited reduced levels of Klotho protein (Q4: -88.77 pg/ml) compared to those in the lowest quartile (Q1) after full adjustment (P = 0.0041). Segmented regression analysis indicated a turning point value of 9.4 in females. Notably, a 1-unit increase in TyG index was significantly associated with a decrease in Klotho levels by -111.43 pg/ml (95% CI: -157.34 to -65.52, P < 0.0001) when TyG index was below 9.4, while above this threshold, the association was not significant (Log likelihood ratio test: 0.009).ConclusionsThe findings highlight a non-linear correlation between the TyG index and serum Klotho concentrations among females, indicative of a saturation effect. This relationship was particularly pronounced in non-diabetic women. In contrast, no statistically significant association was observed in male participants.

Impact of Omega-3 Fatty Acid Supplementation in Parenteral Nutrition on Inflammatory Markers and Clinical Outcomes in Critically Ill COVID-19 Patients: A Randomized Controlled Trial

The heightened inflammatory response observed in COVID-19 patients suggests that omega-3 fatty acids (O3FA) may confer anti-inflammatory benefits. This randomized, double-blind, single-center clinical trial aimed to evaluate the effect of O3FA supplementation in parenteral nutrition (PN) on inflammatory markers in COVID-19 patients admitted to the intensive care unit (ICU). A total of 69 patients were randomized into three groups: one received standard lipid emulsion, and two received O3FA (Omegaven®) at doses of 0.1 g/kg/day and 0.2 g/kg/day, respectively, in addition to Smoflipid®. The primary outcomes measured were serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) on days 1, 5, and 10 of PN initiation. Secondary outcomes included additional inflammatory markers (TNF-α, IFN-γ, IL-1Ra, CXCL10), hepatic function, triglyceride levels, and clinical outcomes such as mortality and length of ICU and hospital stay. Results indicated a significant reduction in CRP, IL-6, and CXCL10 levels in the group receiving 0.1 g/kg/day O3FA compared to the control. Additionally, the higher O3FA dose was associated with a shorter ICU and hospital stay. These findings suggest that O3FA supplementation in PN may reduce inflammation and improve clinical outcomes in critically ill COVID-19 patients.

Эффективность скармливания поросятам-отъемышам кормов с разным уровнем изолейцина и сырого протеина

В статье приведены результаты использования в кормлении поросят-отъемышей полнорационных комбикормов с разными уровнями изолейцина и протеина, а также с различным соотношением аминокислот с разветвленными боковыми цепями (АРЦ), которые обеспечивают получение 236–308 г среднесуточного прироста в послеотъемный период. В исследованиях установлено, что оптимальным соотношением АРЦ (изолейцин/лейцин/валин) является 100/180/140 для рационов с различным уровнем сырого протеина. The article presents the results of research on the use of complete compound feeds in the nutrition of weaning piglets with different levels of isoleucine and protein, and a different ratio of branched-chain amino acids (BCAA), which make it possible to obtain average daily gains in the post-weaning period — 236–308 g. The results of the study suggest that the optimal ratio of BCAA (isoleucine/leucine/valine) is 100/180/140, for diets with different levels of crude protein.

An adenosinergic positive feedback loop extends pharmacological cardioprotection duration.

Adenosine receptor activation induces delayed, sustained cardioprotection against ischaemia-reperfusion (IR) injury (24-72 h), but the mechanisms underlying extendedcardioprotection duration remain unresolved. We hypothesized that a positive feedback loop involving adenosine receptor-induced proteasomal degradation of adenosine kinase (ADK) and decreased myocardial adenosine metabolism extends the duration of cardioprotection. Mice were administered an ADK inhibitor, ABT-702, to induce endogenous adenosine signalling. Cardiac ADK protein and mRNA levels were analysed 24-120 h later. Theophylline or bortezomib was administered 24 h after ABT-702 to examine the late roles of adenosine receptors or proteasomal activity, respectively, in ADK expression and cardioprotection at 72 h. Coronary flow and IR tolerance were analysed by Langendorff technique. The potential for continuous adenosinergic cardioprotection was examined using heterozygous, cardiac-specific ADK KO (cADK+/-) mice. Cardiac ADK expression was also examined after A1 or A3 receptor agonist, phenylephrine, lipopolysaccharide or sildenafil administration. ABT-702 treatment decreased ADK protein content and provided cardioprotection from 24 to 72 h. ADK mRNA upregulation restored ADK protein after 96-120 h. Adenosine receptor or proteasome inhibition at 24 h reversed ABT-702-induced ADK protein deficit and cardioprotection at 72 h. cADK+/- hearts exhibited continuous cardioprotection. Diverse preconditioning agents also diminished cardiac ADK protein expression. A positive feedback loop driven by adenosine receptor-induced ADK degradation and renewed adenosine signalling extends the duration of cardioprotection by ABT-702 and possibly other preconditioning agents. The therapeutic potential of continuous adenosinergic cardioprotection is demonstrated in cADK+/- hearts.

Evaluation of probiotic efficacy of indigenous yeast strain, Saccharomyces cerevisiae Y-89 isolated from a traditional fermented beverage of West Bengal, India having protective effect against DSS-induced colitis in experimental mice.

Increasing awareness regarding health promotion and disease prevention has driven inclusion of fermented foods and beverages in the daily diet. These are the enormous sources of beneficial microbes, probiotics. This study aims to isolate yeast strains having probiotic potential and effectivity against colitis. Initially, ninety-two yeast strains were isolated from Haria, an ethnic fermented beverage of West Bengal, India. Primary screening was done by their acid (pH 4) and bile salt (0.3%) tolerance ability. Four potent isolates were selected and found effective against Entamoeba histolytica, as this human pathogen is responsible to cause colitis. They were identified as Saccharomyces cerevisiae. They showed luxurious growth even at 37 oC, tolerance up to 5% of NaCl, resistance to gastric juice and high bile salt (2.0%) and oro-gastrointestinal transit tolerance. They exhibited good auto-aggregation and co-aggregation ability and strong hydrophobicity. Finally, heat map and principal component analysis revealed that strain Y-89 was the best candidate. It was further characterised and found to have significant protective effects against DSS-induced colitis in experimental mice model. It includes improvement in colon length, body weight and organ indices; reduction in disease activity index; reduction in cholesterol, LDL, SGPT, SGOT, urea and creatinine levels; improvement in HDL, ALP, total protein and albumin levels; decrease in coliform count and restoration of tissue damage. This study demonstrates that the S. cerevisiae strain Y-89 possesses remarkable probiotic traits and can be used as a potential bio-therapeutic candidate for the prevention of colitis.

Hepatic and immune modulatory effectiveness of lactoferrin loaded Selenium nanoparticles on bleomycin induced hepatic injury

This study aimed to estimate the hepatic and immune ameliorating potential of extracted bovine lactoferrin (LF), Selenium nanoparticles (SeNPs) or their combination (LF/SeNPs) against bleomycin (BLM) induced hepatic injury. Fifty adult male rats (160–200 g) were equally divided into five groups: (1) the saline control group, (2) BLM-injected (15 mg/kg twice a week, ip), and (3–5) groups treated orally with LF (200 mg/kg/day), SeNPs (0.0486 mg/kg/day) or LF/SeNPs combination (200.0486 mg/kg/day) for 6 weeks post BLM-intoxication. Blood and liver samples were subjected to biochemical, histopathological, and immunohistochemical analyses. The results revealed that BLM caused a significant increase in hepatic lipid peroxidation and nitric oxide, as well as serum markers of liver functions (AST, ALT and GGT activities), and levels of GM-CSF, CD4, TNF-α, IL-1β, TGF-β1, fibronectin, triglycerides, cholesterol and LDL-C. Additionally, hepatic glutathione, Na+/K+-ATPase, and glutathione peroxidase, as well as serum HDL-C, total protein and albumin levels were significantly reduced. Moreover, BLM injection resulted in marked histopathological alterations and severe expression of caspase 3. Post-treatment of BLM-intoxicated rats with LF, SeNPs or LF/SeNPs combination obviously improved the BLM-induced hepatic damages; this was achieved from the marked modulations in the mentioned parameters, besides improving the histopathological hepatic architecture. It is worth mentioning that LF/SeNPs exerted the greatest potency. In conclusion, the obtained results demonstrated that LF, SeNPs and LF/SeNPs succeeded in attenuating the BLM-induced hepatic dysfunction. Therefore, these supplements might be used to protect against drug-associated side effects.